Adult Stem Cells for Therapy of Visual Disorders

描述（由申请人提供）：没有什么比用“干细胞”重建受损视网膜的可能性更能吸引视力受损患者或治疗他们的眼科医生的想象力了。干细胞被定义为能够分化成多种细胞类型的多能细胞，可以从早期胚胎或成人中获得，并且在适当的条件下，可以分化成多种组织。干细胞已经在脐带血和成人骨髓中被发现，它们代表了一个祖细胞库，可以提供维持各种组织类型的细胞，以及在损伤或应激后抢救/修复受损组织。这些成体干细胞可能在视网膜血管疾病甚至遗传性视网膜变性的治疗中具有广泛的应用价值。虽然在缺血性视网膜病变中使用这些细胞靶向新生血管并有助于稳定脆弱的血管似乎是直观的，但最近观察到的相关神经营养效应（Otani等人，2004年）令人惊讶，但鉴于新出现的范式描述了局部血管网络和视网膜之间存在的营养“互扰”，这是合理的

DESCRIPTION (provided by applicant): Nothing more dramatically captures the imagination of the visually impaired patient or the ophthalmologist treating them than the possibility of rebuilding a damaged retina with "stem cells." Defined as pluripotent cells capable of differentiating into a variety of cell types, stem cells can be derived from early embryos or adults and, under appropriate conditions, will differentiate into a variety of tissues. Stem cells have been identified in cord blood and adult bone marrow and represent a pool of progenitor cells that may serve to provide cells that maintain various tissue types as well as rescue/repair damaged tissue following injury or stress. These adult stem cells may have wide utility in the treatment of retinal vascular diseases and even inherited retinal degenerations. While the use of these cells to target neovasculature and contribute to the stabilization of otherwise friable vessels in ischemic retinopathies may seem intuitive, an associated neurotrophic effect observed recently (Otani, et al, 2004) is surprising but reasonable given newly emerging paradigms describing the existence of trophic "cross-talk" between local vascular networks and the tissues they supply. Thus, potential applications of these cells includes not only cell based therapeutic delivery of various trophic and static substances, but also as stabilizing elements in an otherwise unstable neovasculature of the type observed in ischemic retinopathies. In this proposal we will apply emerging technologies in stem cell biology, gene therapy, proteomics, large scale genomic analysis and live cell imaging to develop stem cell-based therapies for the treatment of vascular and degenerative diseases of the retina. This will be accomplished by (1) identifying and isolating a fraction of progenitor cells from adult bone marrow and cord blood that will target diseased vasculature in the retina and exert trophic rescue effects in animal models of retinal vascular and degenerative disease; (2) determining the mechanism whereby these trophic effects are achieved; (3) engineering a process for the preparation and characterization of the functional cell fraction; and (4) conducting the necessary pre-clinical pharmacological, toxicological and pharmacokinetic studies to take this approach into the clinics. If successful, these studies will lead to a novel therapeutic paradigm for currently untreatable vascular and degenerative diseases of the retina.